Project Leader:

Dr. Qiang Liu

Hepatitis C virus (HCV) is a positive, single-stranded RNA virus in the Flaviviridae family. While HCV infections can be cleared in some infected individuals, they become persistent in the majority of infected people. There is evidence suggesting that the outcome of HCV infections is determined by complex virus-host interactions. Research at VIDO continues to focus on developing vaccines and studying viral pathogenesis.

Background:
A large population is affected by hepatitis C worldwide. In Canada, it is estimated that 240,000 people are infected with the hepatitis C virus and the number is predicted to rise in the next 10 years. There is no vaccine against hepatitis C and the current therapy is very costly and ineffective in about half of the patients.

The outcome of hepatitis C virus infections is determined by complex interactions between the incoming viral pathogen and the host immune defence system. However, the mechanisms underlying HCV-associated immunopathogenesis are poorly understood.

Our major objectives are to develop vaccines against hepatitis C and to study HCV-associated pathogenesis.

Objectives:
• To develop DNA-based vaccines against hepatitis C.
• To develop dendritic cell-based vaccines against hepatitis C.
• To study the pathogenesis of the hepatitis C virus.

Progress:
We optimized the CpG content of an HCV NS3 DNA vaccine at 24 copies of CpG motifs, which induced stronger Th1-type immune responses in mice compared to other frequencies of CpG motifs. A vaccination strategy composed of HCV NS3 DNA vaccine-priming and boosting with NS3 protein formulated with Quil A and CpG oligonucleotides induced strong, Th1-Th2 balanced immune responses in mice. In pigs, vaccination with the HCV NS3 DNA vaccine or with the NS3 DNA vaccine priming followed by NS3 protein boosting induced strong and sustained NS3-specific cellular responses, whereas DNA vaccine-priming and protein-boosting or NS3 protein vaccine induces strong antibody responses.

VIDO is a member of the National Canadian Research Training Program in Hepatitis C.

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